Production of dihalocarbene adducts



excellent method is to add an excess United States Patent 3 265 744PRODUCTION OF DI HAiOCARBENE 'ADDUCTS Gene C. Robinson, Baton Rouge, La,assignor to Ethyl Corporation, New York, N.Y., a corporation of VirginiaNo Drawing. Filed Sept. 7, 1962, Ser. No. 222,173

8 Claims. (Cl. 260-648) reagents. Another method comprises reactingpotassium hydroxide and chloroform inan aqueous mediumand in thepresence of cyclohexene. The reported yield of dichloronorcarane was0.55 percent. sion see The Addition of Dichlorocarbeneto Olefins" byDoering and Hoiiman, Journal of the American Chemical Society, vol. 76,1954, page 6162 et seq.

An examination of the prior art will disclose that the previously knownprocesses are generallycharacterized by low yields or the use ofexpensive reagents. Accordingly, it is an object of thisinvention toprovide the art with a novel process involving the generation ofdihalocarbene which is attractiveboth from the standpoint of yieldsobtained and process economics.

This object is accomplished by reacting together a mixture comprising analkali metal hydroxide, a haloform,

and a dihalocarbene acceptor in a cyclic sulfone solvent. The aforesaidreagents and solvent, as initially charged into'the reaction zone are tobe essentially anhydrous. In other words, an aqueous solvent is notemployed 'in the present process, and more importantly, the 'reactionsystem is essentially anhydrous at the outset. This latter featureappears to enable the reaction to commence.

' Once the reaction has started, the halocarbene produced appears toreact so quickly with the halocarbene acceptor which is co-present thatit is unnecessary to remove the by-product water from the reactionscene. a

The yields of the desired adducts produced pursuant to this inventionhave reached higher than 70 percent. It definitely appears that thesulfone solvent is at least partly responsible for these very beneficialresults. Furthermore, these good yields are achieved utilizing cheap andreadily available reactants. It is interesting to compare these resultswith'the 0.55 percent yield reported by Doering and Hoffman whoattempted to make use of potassium hydroxide as a basic reagent in adihal'o'carbene synthesis. I 1

When carrying out the process of this invention it is necessary toemploy initially essentially anhydrous reagents and solvent. Adistinctly preferred embodiment of this invention is to employ a meansto minimize the effect of water which may initially be present as atrace impurity in the reagents and solvent andalso the water which isgenerated by the reaction itself. A wide variety of methods may beemployed to effect this result. An of the alkali metal hydroxide to thereaction system in order to reduce the efiective water concentration. Ofcourse, when desired, otherdesiccants which are inert to the reactionmass may be added thereto, e.g., silica gel, asbestos, charcoal, and

- the like. Another desirable method is reflux drying which isaccomplished either by gravimetric entrapment of the water in the refluxreturn or by bringing the reflux va- For further discus- "ice pors intocontact with a desiccant or both. Materials which may be used to dry thereflux are phosphorus pentoxide, magnesium perchlorate, alkali andalkaline earth metal hydroxides, aluminum oxide, sulfuric acid,magnesium oxide, beryllium perchlorate, calcium oxide, calcium bromide,calcium chloride, zinc chloride, zinc bromide, copper sulfate, silicagel, charcoal, asbestos, and the like. Excellent results are achievedwhen both reflux drying and an in situ desiccant is employed. Apreferred embodiment of this einventio'n both from the standpoint ofsimplicity and economics comprises the use of an excess of the metalhydroxide reagent as the in situ desiccant.

The alkali metal hydroxides to be employed in this process are lithiumhydroxide, sodium hydroxide, potassium hydroxide, rubidium hydroxide,and cesium hydroxide. These alkali metal hydroxides may be employedindividually or in admixture. The preferable hydroxides for thisreaction are sodium hydroxide and potassium hydroxide. With regard bothto optimum reactivity and cost effectiveness the use of sodium hydroxideis a particularly preferred embodiment of this invention;

The metal hydroxide reagent may be employed in stoichiometricquantities, Le, a molar ratio of hydroxide to haloform of 1:1, however,it is preferred that an excess be used due bothto the desirabilityofdecreasing the effective concentration of water generated by thereaction and and to insure the efiicient consumption of the haloform. Aneffective molar ratio of the-hydroxide to the about 5:]. A particularlyelfective molar ratio is from a about 2:1 to about 4:1.

It is preferred, though not required, that the metal hydroxide beemployed in finely divided form (i.e., the average particle size shouldrange from about 50 to about 500 microns). This can be accomplished insitu by high speed stirring or the hydroxide as initially charged can befinely divided.

The haloforms which are to be used in this reaction are those having atleast 1 atom of chlorine or bromine. Examples of these haloforms arechloroform, bror'noform, dichlorobromoform, dibromochlo'roform;difluorochloroform, dichlorofluoroform, dibromofiuoroform,diiodochloroform, di'chloroiodoform, diiodobromoform,chlorobromoiodoform, fiuorochloroiodoform, fiuorobromoiodoform, and thelike. The various haloforms mentioned above may be used individually orin admixture in this process, however, particularly from the commercialstandpoint, chloroform and bromoform are preferred. The use ofchloroform in all respects is very advantageous.

As was stated above, a cyclic sulfone solvent is to be thereactionmedium for the process of this invention. Whereas a wide variety ofcycloparafiinic sulfones may be used to advantage in this invention, ithas been discovered that the ratio of carbon atoms to sulfone groups inthe molecule has a significantelfect and if maximum yields and shortreaction times are to be achieved it is recommended that the sulfonesolvent chosen has a carbon atom to sulfone group ratio of less thanabout 1021. Examples of these sulfones are trimethylene sulfone',tetramethylene sulfone, pentamethylene sulfone, hexamethylene sulfone,octamethylene su1fone,- decamethylene sulfone, and the like. Sulfoneshaving alkyl substituted rings may also be used, e.g.,3-methyl-l-thiacyclopentane- 1,1-dioxide; 3-methyl 4 ethyl 1thiacyclopentane-1,1- dioxide; 3,4 methyl l thiacyclopentane1,1-dioxide; 4-methyl 1 thiocyclohexene 1,1-dioxide; and the like. It isrecommended that the branched chains in the substituted sulfones have nomore than 5 or 6 carbon atoms and preferably no more than 2 or 3.Sulfones containing a multiplicity of sulfone groups in the ring maylike- 3 wise be employed, for example 1,4 dithiacyclohexane-1,1,4,4-tetraoxide, and the like. ing unsaturated carbon to carbon bondsmay also be useld, e.g., 3,4-ene-3-methyl-l-thiacyclopentane 1,1dioxidie, thianaphthalene dioxide, and the like, however, due to thefact that carbon to carbon multiple bonds serve generally asdihalocarbene acceptors, thesei'sulfones would be used only when theyare also the desired acceptor.

Of the above described group, sulfones having a ratio of carbon atoms tosulfone group of less than about 8:1

are preferred and especially those having a ratio of carbon atoms tosulfone groups of from about 3:1 to about 6:1. An exceptionallypreferred sulfone due both to yields obtained and sulfone.

The use of the above described sulfone solvents and particularly thepreferred solvents is a unique feature of this invention in that it hasproven to dramatically increase yields and reaction rates. In otherwords, the sulfone serves as a catalyst as well as a solvent. Indemonstration of this, when this process is carried without a sulfonesolvent the yields range up to 45 percent and the reaction period is inthe range of 10 to 14 hours whereas when a sulfone solvent is employed(e.g., tetramethylene sulfone) yields range up to 77- percent and usualreaction periods are in the neighborhood of 1.25 hours.

The quantity of sulfone solvent employed in relation to the quantity ofhydroxide is significant and if best results are to be achieved it isrecommended that the molar ratio of sulfone to hydroxide in the reactionsystem should be above about 0.1:1. A preferred molar ratio o'f sulfoneto hydroxide has been found to be'within the range of from about 0.5 :lto about 10:1. A particularlyeffective range is from about 1:1 to about:1.

The sulfone may be employed in this process either in pure form or itmay be cut with other solvents which are inert to the. reaction system.Examples of suitable solvents are hexane, heptane, cyclohexane,petroleum ether, petroleum spirit, kerosene, and the like. "The exactconcentration of sulfone in this solvent mixture is not too important aslong as the molar ratio of sulfone to hydroxide remains within theranges stated above. However, it is recommended that extreme dilution ofthe sulfone should be avoided and best results are achieved when theconcentration of sulfone is above about 20 percent by volume of themixture.

Due to the highly reactive nature of dihalocarbene it is desirable toreact it proximately as formed with a material with which it is capableof forming an adduct. This is preferably accomplished in situ, i.e.,charging the reactor initially with a dihalocarbene acceptor. Thedihalocarbene acceptors cover a very wide range of chemical compoundsandgenerally will comprise organic compounds having up to 25 or morecarbon atoms containing the aliphatic double bond, the aromatic doublebond in a condensed ring nucleus, the carbon tocarbon triple bond, thecarbon-to nitrogen double bond, the carbon to nitrogen tn'ple bond, andpolymers having a multiple bond as part of the repeating unit. Thefollowing are exemplary of compounds capable of forming an adduet withdihalocarbene.

Ethylene, propylene, hutene-l, cis-butene-2, trans-butene-Z,isobutylene, diisobutylene, propylene trimer, propylene tetramer,cyclohexene, cyclooctene, cyclopentene, cyclooctadiene-l,5,cyclooctadiene-l,3, bicycloheptene, bieycloheptadiene, anethol,butadiene, isoprene, chloroprene, camphene, styrene, divinylbenzene,alpha-methylstyrene, propylbenzene, allylbenzene, biallyl,dicyclopentadiene, cyclopentadiene, methylcyclopentadiene,methylcyclopentadiene dimer, dihydropyran, dipentene, vinyl chloride,triisobutylene, vinyl butyl ether, vinyl ethyl ether, vinylidenechloride, alpha-pinene, beta-pinene, tetramethylene-2,5-dihydrofuran,diallylether, 4-methylpentene-1, pentene-l, pentene-Z, Z-methylbutene-l,Z-methylbutene- 2, 3-methylpentene-l, 3-methylpentene-2, hexene-l, hex-Cyclic sulfones containprocess economics is tetramethylene' ene-Z,octene-l, octene-2, octene-3, decene-l, dodecene-l, tetradecene l,octadecene-l, hexadecene-l, cholestene, 4- vinylcyclohexene-l, acroleindiethyl acetal, Z-ethylhexenel, indene, stilbene, dimethyl ketene,acetal, diethyl ketene acetal, vinylacetylene, l-ethyl-l-butylethylene,glycerol triallyl ether, glycerol trivinyl ether,1,5,9-cyclododecatriene, cyclooctatetraene.

Anthracene; l-methoxynaphthalene, Z-methoxynaphthalene,9-methoxyphenanthrene, phenanthrene, acenaphthylene.

Methyl amine, ethyl amine, propyl amine, allyl amine, ethanolamine,aniline, p-toluidine, m-toluidine, o-toluidine, alpha-naphthyl amine,beta-naphthyl amine, p-anisidine, cyclohexylamine.

Benzalaniline, benzalazine, diethylcarbodiimide.

Acetylene, methylacetylene, hexyne-3, butyne-l, butyne- 2,pheuylacetylene, cyclodecyne, diphenylacetylene.

Oleic acid, undecylenic acid, crotonic acid, cinnamic acid, methyl vinylketone, mesityl oxide, acrylic acid, methacrylic acid, acrylonitrile,benzalacetone, dibenzalacetone.

Ally] alcohol, crotyl, alcohol, methyl vinyl 'carbinol, cinnamylalcohol, 3-butene-1-ol.

The nature and identity of a wide variety of dihalocarbene acceptors areknown in the art. For instance, reference may be had to Journal of theAmerican Chemical Society, vol. 76, page 6162 (1954), vol. 81, page 2579(1959), vol. 83, page 603 (1961), vol. 82, page 4085 (1960).

Equimolar amounts of the dihalocarbene acceptor and the haloform may beemployed, however, it is usually desirable to employ an excess of theacceptor. Generally, good results will be obtained when the molar ratioThis process may be conducted at atmospheric pressure.

in an open vessel or an autogenous pressure in a closed vessel. When thedihalocarbene acceptor is a gas under the reaction conditions pressurewill generally be required. The exact temperature for this processdepends, of course, on the particular reagents used, generally, however,good results will be obtained when the temperature is Within the rangeof from 0 C. to about 250 C. The recommended operating temperature rangeis from about 20 to about 110 C. In general, the reaction will becomplete in from about 30 minutes to about 4 hours depending on theprocess conditions. Usually a reaction time of from about 30 minutes toabout 1.25 hours is sufficient.

The following examples illustratethe process of this invention.

Example I Into a. dry reaction vessel equipped with a stirrer and acondenser was charged 25 milliliters of tetrarnethylene sulfone, 0.5mole of chlonoform, 0.25 mole of cyclohexene and 1.00 mole of sodiumhydroxide in commercially available pellet form. The reagents andsolvent were substantially anhydrous as initially charged into thereaction zone. The reaction mixture was heated to 95 C. and stirredslowly. The sodium hydroxide remained substantially in pellet form and asufficient excess thereof had been charged to minimize the effect of thewater generated by the reaction. The reaction was complete in 1.25hours. The yield of dichloronorcarane was 77 percent.

Example II Into the reaction vessel described in Example I was changed25 milliliters of tetramethylene sulfone, 0.25 mole of chloroform, 0.25mole of cyclohexane and 1.00 mole of sodium hydroxide in commerciallyavailable pellet form. The reagents and solvent were substantiallyanhydrous as initially charged into the reaction zone. The reactionmixture was heated to C. with slow stirring. The sodium hydroxideremained substantially in pellet form and a charged to minimizev theeffect of the water generated 'by the reaction. The reaction wascomplete in 1.50 hours and the yield of dichloronorcarane was 70percent.

sufiieient excess thereof had been action by charging the reactor with amolar excess of sodium hydroxide over the moles of chloroform employed,the molar ratio'of sodium hydroxide to chloroform thus being greaterthan 1:1.

TABLES-SUMMARY EXAMPLlESdII-IX WHICH UTILIZE THE GENERAL PROCEDURES OFEXAMPLES I AND II lEx. 'Sultone Hydroxide Haloform Acceptor Temp. TuneAdducts 1 i 1 C.) (Hrs) III. 3methyl-1-thiacyclopentane-l,l- NaOII CHC1Tetrainet-hyl 90 1.20 1,1-dicliloro-z,2,3,3-tetramethyl dioxide.ethylene. 'cyclopropane.

IV Octamethylene sullone... KOH CHBr; Cyclohoxene.... 90 1.25Dihromonorcnrane.

V 'Ietramethylene sulfone.. CsOH CHCI; Ethylene 1.251,1-dichlorocyclopropanc.

. VI. Pentamethylene sulfone NaOH CHF2Cl-.. Pr0pyleuo'-.... 3O 1.1,1-difluoro-2-methylcyclopropane.

V1I. 1,i-dithiaeyclohexunc'l,1,4,4 LiOH CHBrCh... Isobutyleue 30 1.501,1-dicliloro-2,Z-dimethylcyclotetraoxide. propane.

VIII... Hoxamethylene sulfone KOH CHCli Styrene 150 1.50Z-phenyl-l,l-dichlorocyclopropnne.

IX. Tetramethylene sullone ..,Na0H CHCh 1-hexene.... 1. 50Z-nutyl-i,l-diohloroeyclo ropane.

1 Elevated pressures required. All runs are conducted under initiallyanhydrous conditions and with an excess of hydroxide.

The art suggests many uses for adducts of dihalocarbene, for instance,the Journal of the American 20 Chemical Society, vol. 81', page 2579(1959) discloses that the adducts formed from ketene acetals are readilypyrolyzed to alpha-chloroacrylic esters. I Also in the Jourthecyclopropane adduct.

What I claim as new and desire to secure 'by Letters Patent of theUnited States is as follows:

l 1. A process involving the generation of dihalocarbene and theproximate formation of dih-alocanbene adducts which comprises the stepof reacting together an initially essentially anhydrous mixture of analkali metal hydroxide, a haloform, and a dihalocar-bene acceptor inacyclic sulfone solvent for the organic components of said mixture; saidhalof-orm containing at least 1 halogen atom selected from the groupconsisting of chlorine and bromine and said sulfone having a ratio ofcarbon atoms to sulfone groups of less than about 10:1 and beingselected from the group consisting of (1) thiacycloalkane dioxide, (2)dithiacycloalkane, and (3) thiacycloalkene dioxide.

2. The process of claim 1 wherein said ratio of carbon atoms to sulfonegroups is less than about 8: 1.

3. The process of claim 1 wherein said sulfone is tetrarnethylenesulfone.

4. A process involving the generation of dihalocar-bene andthe proximateformation of di halocarbene adducts which comprises reacting together aninitially essentially anhydrous mixture of sodium hydroxide, chloroform,and a dihalocarbene acceptor in tetramethylene sulfone solvent for theorganic components of said mixture; and minimizing the efiect of thewater generated in the re- 5. The process of claim 4 wherein the averageparticle size of the sodium hydroxide is in the range of from about 50to about 500 microns.

6. A process involving the generation of dihaloc-arbene and theproximate formation of dihalocarbene vadduots which comprises the stepof reacting together at a temperature within the range of from about 0C. to about 250 C. an initially essentially anhydrous mixture comprisingan alkali metal hydroxide, a haloform and a dih-alocanbene acceptor in acyclic sulfone solvent: said halofo-rm containing at least one halogenatom selected from the group consisting of chlorine and bromine and saidsulfone having a ratio of: carbon atoms to sulfone groups of less thanabout 10:1 and being selected from the group consisting of (1)thiacycloallea-ne dioxide, (2) dithiacycloalk ane, and (3)thiacycloalkene dioxide.

7. The process of claim 1 wherein said metal hydroxide is sodiumhydroxide and said haloform is chloroform and wherein said dihalocarbeneacceptor contains at least one aliphatic double bond.

8. A process for the preparation of dihalocar bene add'ucts whichcomprises eiiecting a reaction between finely divided sodium hydroxideand chloroform at a temperature in the range of from about 20 C. toabout C. in an initially anhydrous cyclic sulfone reaction mediumadditionally containing, a dih alocarbene acceptor, and the the oarbon-to-nitrogen triple bond, said sulfone having a ratio of carbon atomsto sulfone groups of from about 3:1 to about 6:1 and being selected fromthe group consisting of (1) thiacycloalkane dioxide, (2)dithiacycloalkane, and (3) thiacycloalkene dioxide, the molar ratio ofthe sodium hydroxide to the chloroform being within the range of fromabout 1.5:1 to about 5:1.

References Cited by the Examiner Doe'ring et al., J. Am. Chem. Soc, vol.76, pp. 6162- 64 (1954). LEON ZITVER, Primary Examiner.

K. H. JOHNSON, K. V. ROCKEY, Assistant Examiners.

1. A PROCESS INVOLVING THE GENERATION OF DIHALOCARBENE AND THE PROXIMATEFORMATION OF DIHALOCARBENE ADDUCTS WHICH COMPRISES THE STEP OF REACTINGTOGETHER AN INITIALLY ESSENTIALLY ANHYDROUS MIXTURE OF AN ALKALI METALHYDROXIDE, A HALOFORM, AND A DIHALOCARBENE ACCEPTOR IN A CYCLIC SULFONESOLVENT FOR THE ORGANIC COMPONENTS O SAID MIXTURE; SAID HALOFORMCONTAINING AT LEAST 1 HALOGEN ATOM SELECTED FROM THE GROUP CONSISTING OFCHLORINE AND BROMINE AND SAID SULFONE HAVING A RATIO OF CARBON ATOMS TOSULFONE GROUPS OF LESS THAN AOUT 10:1 AND BEING SELECTED FROM THE GROUPCONSISTING OF (1) THIACYCLOALKANE DIOXIDE, (2) DITHIACYCLOALKANE, AND(3) THIACYCLOALKENE DIOXIDE.